Stroke—A Primer

A stroke—disrupted circulation that kills brain tissue—can devastate the brain, leaving neurological impairments including paralysis, partial or total loss of language, and severe cognitive deficits. In the United States, stroke is the third leading cause of death.

Some strokes are relatively minor, causing little if any lasting damage. And although they are sudden, the brain injury strokes inflict often evolves over the course of hours or even days. Prompt, effective treatment can mean the difference between a good recovery and permanent disability or death.

What Is a Stroke?[i], [ii]
Ischemic strokes, which occur when blood flow to part of the brain is blocked by a clot, are most common, accounting for 80% of the total.

The clot may originate in the heart (cardioembolic stroke), often due to disturbed heart rhythm, and travel through the bloodstream to lodge in a cerebral artery. Or it may result from atherosclerosis—a clot forms and breaks off from arterial plaques of fatty material within or outside the brain. Atherosclerosis can also increase a brain artery’s vulnerability to blockage by making it more narrow.

The effects of stroke depend on the location of the blockage. A clot in a large artery to one side of the brain may cause weakness, paralysis, or sensory loss on the opposite side of the body, and possibly loss of speech. If it occurs in an artery supplying the back of the brain, dizziness, memory loss, and gait and swallowing disturbances are common.

Occlusion of a small artery deep in the brain (a lacunar stroke) may have more limited consequences.

Hemorrhagic strokes are less common, but more often severe or deadly. Here, a ruptured blood vessel bleeds into the brain itself (intracerebral hemorrhage) or into the space between the brain and the skull (subarachnoid hemorrhage). In most cases of intracerebral hemorrhage, the artery wall has been weakened or damaged by chronic high blood pressure. The usual cause of subarachnoid hemorrhage is an aneurysm—a weak spot in the artery wall that balloons out and ultimately thins to the point of rupture.

Because hemorrhagic strokes often affect large parts of the brain, the consequences are frequently widespread and worsen rapidly.

The Ischemic Cascade[ii], [iii], [iv]Brain injury from an ischemic stroke is the result of a complex molecular process.

Without sufficient glucose and oxygen, the neuron cannot generate energy to maintain proper chemical balance, and excessive calcium and sodium enter the cell body. This triggers the release of excitatory neurotransmitters, particularly glutamate, which allow more positive ions to accumulate.

The destructive cascade of molecular events continues as calcium activates proteolytic enzymes (that break down proteins) and inflammatory mediators; the neurons and surrounding glial cells swell with water, their membranes and internal structures deteriorate, and they die.

Brain cells in the area where blood supply is cut off nearly completely—the ischemic core— succumb in minutes. But there is usually a broader zone of moderately impaired circulation—the penumbra—where neurons may remain dysfunctional for hours or even days but survive and return to normal if blood supply is restored before the ischemic cascade causes irreversible damage.

If the stroke is severe, however, destruction can spread further. Fluids accumulate around injured tissue (edema), compressing the brain, disrupting nerve tracts and arteries, and creating wider areas of ischemia.

After an ischemic stroke, as blood flow to the damaged area is restored (whether by treatment or through collateral circulation), some bleeding (hemorrhagic conversion) is inevitable. This is harmless if limited, but if pronounced, can cause further damage.

Hemorrhagic Stroke Damage[v], [vi], [vii]
The molecular processes behind hemorrhagic stroke damage to the brain are less well understood.

The initial symptoms of intracerebral hemorrhage result from brain irritation by blood that has escaped from ruptured vessels. As the mass of blood (hematoma) grows, increasing pressure within the brain injures tissue by compression and displacement. Subarachnoid hemorrhage, trapped under the inelastic skull, exerts similar pressure on the brain.

Processes set in motion by hemorrhage can cause further injury in subsequent hours and days. The chemical thrombin, produced in the body’s attempt to form clots and stop the bleeding, is toxic to the brain in large quantities. It promotes edema that increases pressure on brain tissue, possibly by opening the blood-brain barrier.

Red blood cells within the hematoma break down and release iron, worsening edema and injuring brain cells by oxidation.

After subarachnoid hemorrhage, the pressure of the hematoma and edema can irritate major arteries, causing vasospasm, sudden blood vessel constriction that produces significant ischemia within the brain weeks after the initial stroke.

Acute Treatment[i], [iii], [iv], [v], [viii], [ix], [x]

Time is of the essence. Stroke symptoms—sudden dizziness, confusion, severe headache, difficulty speaking, double vision, weakness, numbness or paralysis of an arm, leg or face, especially on one side—demand immediate medical attention.

Ischemic and hemorrhagic stroke need very different treatment, and the first necessity is distinguishing between them. This cannot be done on the basis of symptoms, but requires a CT scan or MRI.

During an ischemic stroke, restoring blood flow can rescue brain tissue in the penumbra from permanent damage, and even revive some cells in the ischemic core. Within the first four and a half hours after symptoms begin, the standard treatment is intravenous tissue plasminogenactivator (tPA), to dissolve the clot.

After four and a half but before eight hours, administration of tPA or another clot-dissolving chemical directly to the brain through an arterial catheter, or removal of the clot with a device threaded through the arteries, may limit brain injury.

In the hours after an ischemic stroke, it is also essential to control blood pressure and blood sugar, and monitor pressure within the brain to detect edema or hemorrhagic conversion.

Immediate treatment of a hemorrhagic strokeis largely supportive—maintain respiration and other vital functions during the danger period—and a matter of keeping blood pressure down to prevent further bleeding.

When hemorrhagic stroke occurs in someone who had been taking an anticoagulant (such as Coumadin), treatment includes vitamin K or drugs to reverse its action. After subarachnoid hemorrhage, a calcium channel blocker can forestall vasospasm.

Depending on the size and location of the hematoma and the degree of edema, surgery to relieve pressure by drilling a hole through the skull or placing a shunt to drain fluid may be indicated.

Risk reduction[xi],[xii]Prevention is better than the best treatment. High blood pressure is a powerful risk factor for both hemorrhagic and ischemic stroke: generally, it should be kept under 140/90 mmHg (below 120/80 is ideal), with a healthy lifestyle and, when necessary, medication as well.

Smokinggreatly increases the risk of both kinds of stroke and must be avoided.

[ii] Internet Stroke Center, a non-profit, educational service supported in part by the NIH Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network, and NINDS grant 3P50NS055977 to Washington University School of Medicine in St. Louis and UT Southwestern Medical Center. http://www.strokecenter.org